Background: Endoscopic retrograde cholangiography (ERC) and tissue sampling (brush cytology and biopsy) are the standard non-surgical techniques for evaluating indeterminate bile duct strictures. The utility of these studies is hindered by their low sensitivity for diagnosing bile duct malignancies. Preliminary data from our group and others have shown that intraductal ultrasound (IDUS), digital image analysis (DIA) and fluorescent in situ hybridization (FISH) may assist in the evaluation. Hypothesis: IDUS, DIA, and FISH significantly enhance the accuracy of standard techniques (ERC with brush cytology and intraluminal biopsy) for the diagnosis of indeterminate bile duct strictures. Aims 1:To determine the accuracy (as assessed by the sensitivity, specificity, positive predictive value, and negative predictive value) of intraductal ultrasound (IDUS), digital image analysis (DIA), fluorescent in situ hybridization (FISH), cholangiography, brush cytology, and biopsy in the evaluation of indeterminate bile duct strictures. 2. To test the hypothesis that the accuracy of the composite results for IDUS, DIA and FISH is better than the composite results for cholangiography, brush cytology, and biopsy in the evaluation of indeterminate bile duct strictures. 3. To combine the results of all studies in a manner that maximizes the accuracy of the diagnosis of indeterminate bile duct strictures. Methods: One hundred patients referred for evaluation of an indeterminate bile duct stricture will undergo ERC, brush cytology, biopsy, IDUS, DIA, and FISH. The sensitivity, specificity, accuracy, PPV, and NPV of each technique will be compared to the patients' final clinical diagnosis (benign or malignant stricture). A forward stepwise procedure will be used to combine the results to develop a decision model. Starting with the most accurate test, each of the other five tests will be combined with the most accurate test and then compared with the most accurate test alone using McNemar's test. The combination with the lowest resulting p-value will form the most accurate combination of two tests. Significance: The study results have the potential to significantly improve the accurate diagnosis of biliary strictures. Earlier and more definitive diagnosis will translate into improved treatment options.